These studies are designed to investigate the effects of TCDD on the biosynthesis and utilization of heme as well as the induction of microsomal cytochromes and related enzyme activities in mammalian liver. TCDD is known to produce teratogenesis and fetal lethality in mammals as well as porphyria in a variety of species. TCDD also increases the activation of various exogenous carcinogenic hydrocarbons and alters the metabolism of endogenous steroid hormones in mammalian tissues. The present studies demonstrate that TCDD induces the de novo synthesis of apocytochrome P-448 which in turn combines with endogenous heme to form the spectrally and enzymatically distinct holocytochrome P-448. Time course studies following acute oral administration of TCDD demonstrate persistent elevation of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase activities for as long as three months after a single treatment of TCDD. As little as 65 molecules of TCDD per hepatocyte (0.002 micron g/kg) caused a signigicant increase in AHH activity. These studies demonstrate a biological basis for the effects of TCDD at very low doses in mammalian liver.